Sexual Orientation: Neuroendocrine and Psychodynamic Influences

In this article we discuss psychoneuroendocrine influences on sexual orientation and the psychodynamics of internalized homophobia. Because of space limitations, we focus on homosexual orientation, although research in this area sheds light on heterosexual and bisexual orientation as well.

NEUROENDOCRINE INFLUENCES

Research that has been conducted on the relationships between hormones and behavior suggests that prenatal hormones might influence sexual orientation in some persons. Although this hypothesis still requires definitive proof, accumulating evidence has ever-increasing clinical significance.1

It has long been recognized that male sex-stereotypical behavior in many animals—mounting, penile insertion, pelvic thrusting—is controlled by the medial preoptic area of the hypothalamus. Female sex-stereotypical behavior—lordosis (arching of the back)—is controlled by the ventromedial nucleus. These hypothalamic nuclei are organized by sex steroid hormones. During a critical period of prenatal or (depending on the species) perinatal life, the male fetal testis secretes androgen, which alters the structure of the hypothalamus, increasing male sex-stereotypical behavior later in development and diminishing female sex-stereotypical behavior. In humans, a testosterone surge occurs between the 8th and 24th week of pregnancy. If no testosterone surge occurs, the brain differentiates as female, and the sex-stereotypical behavior that develops is also typically female—organized around the lordosis response.2-4

It is possible to experimentally manipulate prenatal sex steroid hormones to influence animals to demonstrate both female and male sex-stereotypical responses (lordosis and mounting).5,6 Based on this research, a number of investigators have speculated that human sexual orientation might be influenced by prenatal hormones.7,8

This theory of hypothalamic influence on human sexual orientation has found some support; for example, some girls who are exposed to increased prenatal androgens because of congenital adrenal hyperplasia (CAH) have increased homosexual interest and diminished heterosexual interest later in life. Even though these findings are not robust and most such girls grow up to become heterosexual women, they point in a direction predicted by the prenatal androgen hypothesis.9-11

LeVay12 undertook a study that increased attention to this line of thinking. He observed that a particular hypothalamic nucleus (the third interstitial nucleus of the anterior hypothalamus [INAH 3]) in roughly the same location in humans as the sexual dimorphic nucleus (SDN) of rats was much smaller in homosexual than heterosexual men and, in fact, similar in size to that of women. Because this nucleus is prenatally influenced by androgens, he speculated that the object of sexual interest of rats and humans might be controlled by similar hormone-brain interactions. LeVay studied brain structure, not function, however, and a subsequent attempt to replicate his research by Byne and colleagues13 was suggestive but not conclusive.

More recently Roselli and colleagues14 studied sheep, an animal species in which a small number of males prefer mounting other males to females. These male-oriented rams were shown to differ from female-oriented rams in one particular hypothalamic nucleus. This hypothalamic nucleus was located in roughly the same place as the rat SDN and INAH 3 in humans. However, the researchers emphasized that there was no way of knowing whether these hypothalamic nuclei are homologous across species. They called the sheep nucleus ovine (o)SDN.

However, ancillary evidence was found to strengthen the argument that this hypothalamic nucleus might influence the sexual object of sheep. In the brain, androgens are converted to estrogens, which then act on estrogen receptors to masculinize sexual behavior. The enzyme responsible for this steroid conversion is aromatase. The Roselli group found that messenger RNA levels for aromatase were higher in the oSDN in males than in females, and higher in those rams sexually oriented toward females than those sexually oriented toward males.15

Putting the story together

Among men motivated to have sex with other men, some might simply be expressing behavior prenatally determined by hypothalamic structures formed under the influence of sex steroid hormones whose ebbs and flows happened to differ from those of the mainstream. Although scant, some data do exist to support this theory in humans and to suggest that a similar line of reasoning may be applied to some women.

On the one hand, persons who have same-sex partners are quite diverse, and no psychobiological generalizations about their motivation can possibly be applied to all. On the other hand, the psychoneuroendocrine research only briefly outlined here is undeniably intriguing and, at the very least, indicates that psychiatrists must be cognizant of prenatal hormonal influences on brain structure and function in order to understand sexual behavior.

Prenatal androgen and gender-role behavior

Prenatal androgen also influences gender-role behavior. This is evident from the play patterns of girls with early corrected CAH. These children tend to play more like boys than unaffected girls do. They tend to be tomboys, for example, and enjoy rough-and-tumble activities more frequently than their sisters. Although their childhood gender-role behavior is somewhat boy-like, most of these girls see themselves as female and are not uncertain about their gender identity. Gender identity formation usually is the product of many interacting biological, psychological, and social influences, including intrafamilial relationships.16